Human papilloma virus (HPV) infections of the urogenital tract represent the most often sexually transmitted viral disease in humans (refs. 1 to 3-various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosure of these references are hereby incorporated by reference into the present disclosure). HPV is a double stranded DNA virus and with the recent developed molecular biological techniques, more than 55 different HPV types have been recognized (ref. 4). HPV is associated with a wide spectrum of clinical states including condylomata acuminata, latent and subclinical infection, and Bowen's disease. Subclinical infections gain more importance as they are believed to cause intraepithelial neoplasia, based on the frequent detection of HPV DNA in invasive carcinomas, especially in urogenital region (refs. 1, 5). A significant risk for the development of an invasive cancer is ascribed to the infections by HPV types 16, 18 and 33 (refs. 6 to 9).
The most prevalent HPV types causing condylomata acuminata are type 6 and 11. Condylomata acuminata are visible, multifocal, multicentric and multiform lesions. Predilection sites are penis, scrotum, perineum, urethra, perianal regions, intertriginous zones, and oral mucosa. In uncircumcised men the frenulum, the coronary sulcus and the inner aspect of the foreskin are most often afflicted, whereas in circumcised patients the shaft of the penis is involved. Genital warts are of great psychological and cosmetic relevance representing a major hindrance to sexual performance.
Treatment options include surgical methods like excision, electrocautery, cryosurgery or laser vaporization. It has been shown in molecular hybridization studies that HPV DNA sequences exist in adjacent normal tissue after carbon dioxide laser removal of genital warts (ref. 10). These findings and the well known high recurrence rates after initial treatment demonstrate the need for adjuvant therapy to eradicate invisible disease. Therapeutic results with local application of cytotoxic agents, for example, 5-fluorouracil and podophyllin/podophyllotoxin have, however, been unsatisfactory (refs. 11 to 13). Furthermore, several types of interferons (IFN) as well as autologous vaccines have been tried with varying success (refs. 2, 14 to 17). More recently, oral isotretionin has been given with some success to reduce the recurrence rate (refs. 18, 19, 20).